Nitric oxide (NO) is an endogenous mediator of various physiological functions in the gastrointestinal, genitourinary, cardiovascular, respiratory, and nervous systems. Nitric oxide has long been established as a signaling molecule that promotes relaxation of smooth muscle cells. More recently, it has been established or implicated that NO can mediate other biological processes and diseases including, for example, wound healing, inflammation, plant disease resistance, sexual dysfunction, social dysfunction, cancer, coronary heart disease, restenosis, hypertension and angiogensis. There are also implications of the role of NO in organ perseveration during transplantation and procurement. The implication of NO in so many biological processes and diseases has stimulated interest in its exogenous delivery. However, NO is a diatomic free radical, and its exogenous delivery as a gas to biological systems has proved impractical due to its high reactivity.
A number of systems have been proposed and tested for in situ generation and delivery of NO. Such NO-releasing compounds include chemical compounds such as, for example, diazeniumdiolates, S-nitrosothiols, metal nitrosyl complexes, NO-releasing gold nanoparticles, NO-releasing polyethyleneimine (PEI) fibers and NO-releasing zeolites. For some NO-releasing compounds, the rate of NO release can be varied somewhat through temperature, pH or enzymatic control, although most NO-releasing compounds are non-specific and release NO spontaneously. Poor solubility and generation of potentially toxic byproducts have further stalled the use of NO-releasing compounds for exogenous delivery of NO.
In view of the foregoing, compositions and methods providing for controlled or sustained release of NO would be of substantial benefit in the art. Desirably, such systems would promote controlled or sustained release of NO to exploit the beneficial properties of NO in biological systems, while at the same time minimizing the toxicity or biological incompatibility of present NO-releasing materials.